Shell-Switchable SERS Blocking Strategy for Reliable Signal-On SERS Sensing in Living Cells: Detecting an External Target without Affecting the Internal Raman Molecule.

For SERS analysis in living cells, the inevitable desorption of Raman molecule on the substrate surface is a key challenge. To ensure high stability, SERS systems with Raman molecules protected inside the core-Raman molecule-shell (C-M-S) structures have been designed, but at the expense of sacrificed sensing performances. Here a shell-switchable SERS blocking strategy is developed for the reliable SERS analysis in living cells, relying on the shell blockers to regulate the SERS sensing signal without affecting the internal Raman molecules. After several C-M-S structures were investigated, the SERS blocking mechanism confirmed that thick shells (Au, Ag, ZnO, and MnO2) can cause a significant reduction in the internal SERS signal by obstructing the penetration of the laser or signal. The CAu-Mpy-SAu-SMnO2 nanoprobe is designed for the ratiometric SERS sensing in living cells, which retains sensing performances even though the Raman molecule is protected inside the nanostructure. This SERS strategy makes the turn-on sensing achievable in living cells with the MnO2 shell as a signal switch and a Raman reference. Additionally, it allows for accurate monitoring of the degradation of MnO2 carriers in living cells, even without fluorescent labels.